ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Minying Wu,Jianqiang Yang,Tong Ye,Baoxin Wang,Yi Tang,Xinjiang Ying
Ti3C2Tx MXene is a versatile two-dimensional material that exhibits exceptional properties, such as an abundance of surface functional groups that facilitate modifications. Additionally, Ti3C2Tx MXene possesses remarkable photothermal effects. In this study, ultrathin Ti3C2Tx nanosheets with dimensions (∼200 nm) suitable for biological applications were prepared by ultrasonication of larger pieces of Ti3C2Tx MXene with a cell pulverizer operating at a specific power. The ultrathin nanosheets exhibited a significant photothermal conversion efficiency (47.1%) under an 808 nm infrared laser irradiation. In addition, they showed an excellent mass extinction coefficient of 15.7 L g–1 cm–1. By exploiting the intermolecular force between these ultrathin nanosheets and doxorubicin (DOX), a drug loading efficiency of 72.8% was achieved. Through layer-by-layer surface modification of a sulfhydryl-modified polymethacrylic acid (PMAsh) shell and a transferrin (Tf) layer with targeting function, a multifunctional nanomedicine platform (Ti3C2Tx-DOX-PMAsh-Tf) was constructed. Experiments executed in vitro with cells and in vivo to inhibit tumors manifested that Ti3C2Tx is biocompatible. Furthermore, the results showed that the drug release behavior of Ti3C2Tx-DOX-PMAsh-Tf is responsive to glutathione (GSH) stimulation. The synergistic treatment of photothermal therapy and the anticancer drug DOX effectively achieved the inhibition of human hypopharyngeal squamous cell carcinoma.
研究领域:
生物医学工程
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肿瘤学
·
材料科学
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DOI
PubMed
高影响因子
BMC CANCER
·
2023
·Vol. 23
·期 1
·1-14
·
IF 3.8
Lau Hui-Ching,Yuan Xiaohui,Huang Huiying,Zhang Ming,Hsueh Chi-Yao,Gong Hongli
Background To investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC).Methods The prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2’-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins.Results Fn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH−, which could be proven by H2O2 assay and N-acetylcysteine.Conclusion sHigher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.
研究领域:
肿瘤学
·
微生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CARCINOGENESIS
·
2024
·
IF 3.3
Yang Xin,Cui Limei,Liu Zhonglu,Li Yumei,Wu Xinxin,Tian Ruxian,Jia Chuanliang,Ren Chao,Mou Yakui,Song Xicheng
Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell, and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy, and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared to normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion, and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2013
·
IF 0
Zhisen Shen,Jingjing Chen,Cheng Kang,Changfeng Gong,Yabin Zhu
Porous polymeric scaffolds have been much investigated and applied in the field of tissue engineering research. Poly(ester urethane) (PEU) scaffolds, comprising pores of 1–20 μm in diameter on one surface and ≥200 μm on the opposite surface and in bulk, were fabricated using phase separation method for hypopharyngeal tissue engineering. The scaffolds were grafted with silk fibroin (SF) generated from natural silkworm cocoon to enhance the scaffold’s hydrophilicity and further improve cytocompatibility to both primary epithelial cells (ECs) and fibroblasts of human hypopharynx tissue. Coculture of ECs and fibroblasts was conducted on the SF-grafted PEU scaffold (PEU-SF) to evaluate its in vitro cytocompatibility. After co-culture for 14 days, ECs were lined on the scaffold surface while fibroblasts were distributed in scaffold bulk. The results of in vivo investigation showed that PEU porous scaffold possessed good biocompatibility after it was grafted by silk fibroin. SF grafting improved the cell/tissue infiltration into scaffold bulk. Thus, PEU-SF porous scaffold is expected to be a good candidate to support the hypopharynx regeneration.
研究领域:
组织工程
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生物医用材料
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再生医学
✓ 已验证
产品关联
DOI
PubMed
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2018
·Vol. 50
·期 6
·567-578
·
IF 2.224
Zhang Yingying,Cong Linhai,He Jiayan,Wang Yu,Zou Yingying,Yang Zhihong,Hu Yuexin,Zhang Shiwen,He Xiaoguang
Hypopharyngeal carcinoma (HC) is one of the most malignant tumors in the upper aerodigestive tract. Currently, there are no effective treatments for HC. Gold nanoparticles (AuNPs) are a promising tool that can be used for plasmonic photothermal therapy (PPTT), which refers to the use of electromagnetic radiation, most often in near infrared (NIR) region, for the treatment of various medical conditions including cancer. AuNPs have been proved to be a promising tool for NIR spectroscopy-mediated photothermal therapies. In this study, we chemically conjugated AuNPs with a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR), a cell-surface receptor that is overexpressed in many cancers. We then assessed the effect of NIR photothermal treatment with the EGFRmAb–AuNPs in FaDu HC cells. Our data showed that nanoparticle conjugation with the EGFRmAb improved the specific targeting towards FaDu cells and reduced cytotoxicity towards normal (293 T) cells which do not overexpress the EGFR. A significant amount of our EGFRmAb-conjugated AuNPs could enter the nucleus. Moreover, the expression levels of double strand DNA break repair proteins, including p-ATR, p-CHK1, and p-CHK2 were increased following AuNPs treatment, indicating the presence of DNA damage. These findings suggest that the AuNPs can potentially disrupt genome integrity and induce apoptosis. In addition, EGFRmAb–AuNPs+NIR could induce FaDu cell apoptosis, accompanied by the inhibition of the PI3K/AKT/mTOR pathway and stimulation of DNA damage response. Based on these data, PPTT using the EGFRmAb–AuNPs could be a new promising treatment for HC.
研究领域:
肿瘤学
·
纳米技术
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分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 2
·
IF 6.353
Qiu Shijie,Liang Lijin,Zou Peng,Chen Qi
There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide, and hence growing needs for hypopharyngeal and cervical esophageal tissue repair. This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid, which resembled the layered architectures of its intended tissues. The decellularized small intestine submucosa contained minimal residual DNA (52.5 ± 1.2 ng/mg) and the composite scaffold exhibited satisfactory mechanical properties (a tensile modulus of 21.1 ± 4.8 MPa, an ultimate tensile strength of 14.0 ± 2.9 MPa and a failure strain of 26.9 ± 5.1%). The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays, immunostaining and Western blotting. Desirable cell proliferation and phenotypic behaviors were observed. These results have provided an important basis for the next-step in vivo studies of the scaffold, and bode well for its future clinical applications.
研究领域:
生物医学工程
·
组织工程
·
癌症研究
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER CHEMOTHERAPY AND PHARMACOLOGY
·
2023
·Vol. 92
·期 3
·211-221
·
IF 3
Wang Dongbo,Wu Huina,Wu Qian,Liu Qi,Li Yamei,Wu Jiyong,Nie Jing
Purpose Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer. In recent years, the modification of platinum(II) into platinum(IV) derivative compounds, by introducing biologically active molecules, has been extensively employed to develop novel platinum-based prodrugs. We investigated the anti-proliferative activity against HNSCC of a new veratric acid (COX-2 inhibitor)-platinum(IV) complex. Methods In this study, a new veratric acid (COX-2 inhibitor)–platinum(IV) complex, termed veratricplatin, was synthesized. We evaluated the anti-tumor effect of in vitro and in vivo by western blotting, flow cytometry and DNA damage analysis. Results Veratricplatin displayed remarkable anti-proliferative activity against various cancer cell lines, including A549, FaDu, HeLa, and MCF-7. Furthermore, veratricplatin demonstrated significantly stronger cytotoxicity than either platinum(II) or veratric acid monotherapy or their combination. Importantly, the synthesized prodrug exhibited less toxicity toward normal cells (MRC-5), while dramatically enhanced DNA damage in FaDu cells inducing apoptosis. Moreover, veratricplatin markedly reduced the migration ability of FaDu cells compared to the control or monotherapy. In vivo, veratricplatin displayed potent anti-tumor activity with no apparent toxicity in BALB/c nude mice bearing FaDu tumors. In addition, tissue immunofluorescence analysis revealed that veratricplatin could substantially inhibit the formation of tumor blood vessels. Conclusion Veratricplatin demonstrated remarkable drug efficacy, in terms of increased cytotoxicity in vitro and high efficiency with low toxicity in vivo.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2015
·
IF 1.579
Zhisen Shen,Dakai Lu,Qun Li,Zongyong Zhang,Yabin Zhu
Biodegradable crosslinked polyurethane (cPU) was synthesized using polyethylene glycol (PEG), L-lactide (L-LA), and hexamethylene diisocyanate (HDI), with iron acetylacetonate (Fe(acac)3) as the catalyst and PEG as the extender. Chemical components of the obtained polymers were characterized by FTIR spectroscopy, 1H NMR spectra, and Gel Permeation Chromatography (GPC). The thermodynamic properties, mechanical behaviors, surface hydrophilicity, degradability, and cytotoxicity were tested via differential scanning calorimetry (DSC), tensile tests, contact angle measurements, and cell culture. The results show that the synthesized cPU possessed good flexibility with quite low glass transition temperature (, −22°C) and good wettability. Water uptake measured as high as 229.7 ± 18.7%. These properties make cPU a good candidate material for engineering soft tissues such as the hypopharynx. In vitro and in vivo tests showed that cPU has the ability to support the growth of human hypopharyngeal fibroblasts and angiogenesis was observed around cPU after it was implanted subcutaneously in SD rats.
研究领域:
材料科学
·
组织工程
·
生物材料
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2023
·
IF 4.5
Linlin Zhang,Lei Cheng,Zhemeng Chen,Yi Fang,Changjiang Li,Min Chen,Peijie He,Haitao Wu,Jianzhang Wu,Jian Chen
Hypopharyngeal carcinoma is notorious for its poor prognosis among all head and neck cancers, posing a persistent challenge in clinical settings. The continuous hyperactivation of the NFκB signalling pathway has been noted in various cancer types, including hypopharyngeal carcinoma. In our quest to develop a novel drug that targets hypopharyngeal cancer via the NFκB pathway, we employed curcumin, a well-known lead compound, and performed chemical modifications to create a mono-carbonyl analogue called L42H17. This compound exhibited exceptional stability and displayed an enhanced binding affinity to myeloid differentiation protein 2 (MD2). Consistent with expectations, L42H17 demonstrated the ability to inhibit TNF-α-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), prevent IκB degradation, and subsequently impede NFκB-p65 nuclear translocation in hypopharyngeal cancer cells. Additionally, L42H17 exhibited a remarkable capacity to induce cell cycle arrest at the G2-M phase by inactivating the cdc2-cyclin B1 complex. Moreover, it facilitated cell apoptosis by reducing Bcl-2 levels and augmenting the expression of cle-PARP and cle-caspase3. Importantly, we observed a significant enhancement in the anti-cancer efficacy of L42H17 in a patient-derived tumour xenograft (PDTX) model of hypopharyngeal carcinoma. In conclusion, our findings strongly suggest that L42H17 holds promise as a potential candidate drug for the treatment of hypopharyngeal carcinoma in the future.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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